Hepatocyte nuclear factor-1β is not a specific marker of clear cell carcinoma in serous effusions

Our plain-English summary of Hepatocyte nuclear factor-1β is not a specific marker of clear cell carcinoma in serous effusions, by B. Davidson (Cancer Cytopathology, 2014).

The study

• Author: B. Davidson
• Journal: Cancer Cytopathology
• Published: 2014;122(2):153-8
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The transcription factor hepatocyte nuclear factor-1β (HNF1β) has been reported to be a specific clear cell carcinoma marker, but its role in the diagnosis of serous effusions is largely unexplored. The objective of this study was to assess the diagnostic role of 2 commercial antibodies against HNF1β in effusion specimens.

Methods: Effusions (n = 101), consisting of 43 ovarian adenocarcinomas (26 serous, 14 clear cell, 3 endometrioid), 37 nonovarian adenocarcinomas, 10 malignant mesotheliomas, 2 nonepithelial cancers, and 9 reactive specimens, were immunostained using antibodies from Santa Cruz Biotechnology Inc (Santa Cruz, Calif) and Atlas Antibodies AB (Stockholm, Sweden).

Results: Use of the Santa Cruz antibody was associated with cytoplasmic or background staining in some specimens, whereas distinct staining with minimal background was observed using the Atlas antibody. The Santa Cruz antibody performed better in differentiating clear cell carcinoma from serous ovarian carcinoma and breast carcinoma, whereas staining was consistently negative in benign and malignant mesotheliomas using both antibodies. Distinct nuclear expression of HNF1β was observed in lung and gastrointestinal carcinomas, most often using the Atlas antibody.

Conclusions: The HNF1β antibody from Atlas performed better than its counterpart from Santa Cruz in terms of staining quality, but was less specific for clear cell carcinoma. Although HNF1β may be of diagnostic value in differentiating clear cell from serous carcinoma in cases with proven genital origin, the role of this marker is questionable in the differential diagnosis between the former tumors and adenocarcinomas of other origin, particularly in the setting of metastasis from an unknown primary tumor.

© 2013 American Cancer Society.

In plain English

This single-author study tested whether the protein hepatocyte nuclear factor-1β (HNF1β) helps identify clear cell carcinoma in fluid samples (effusions) from body cavities. The author stained 101 effusions, sent for routine diagnosis to the Norwegian Radium Hospital in Oslo in 1998 through 2005, with commercial antibodies from Atlas Antibodies and Santa Cruz Biotechnology. Samples included ovarian, other gynecologic, breast, lung and gastrointestinal cancers, 10 malignant mesotheliomas and 9 reactive specimens. Both antibodies stained 12 of 14 ovarian clear cell carcinomas. The Atlas antibody stained 5 of 26 serous ovarian carcinomas; the Santa Cruz antibody stained none. Neither antibody stained the malignant mesotheliomas or the reactive mesothelial cells. The Atlas antibody often stained breast, lung and gastrointestinal cancers. The Santa Cruz antibody stained no breast cancers but many lung and gastrointestinal cancers, and produced background staining in some samples. The author concluded that HNF1β may help separate clear cell from serous carcinoma in cancers of proven genital origin, but that its role is questionable against adenocarcinomas of other origin, particularly in metastases from an unknown primary tumor. The study did not look at asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic laboratory (immunohistochemistry) study of archived effusion specimens, comparing two commercial antibodies against HNF1β
• Who was studied: 101 effusion specimens submitted for routine diagnosis to the Department of Pathology, Norwegian Radium Hospital, Oslo, Norway, 1998 through 2005. They comprised 43 ovarian carcinomas (26 serous, 14 clear cell, 3 endometrioid), 6 endometrial and 5 uterine cervical carcinomas, 10 breast, 5 lung and 10 gastrointestinal carcinomas, 10 epithelioid malignant mesotheliomas (4 peritoneal, 6 pleural), 3 other cancers, and 9 reactive specimens. The sites were 59 peritoneal, 41 pleural and 1 pericardial.
• Exposure: Not an exposure study; no asbestos or fiber exposure is reported. The specimens were stained with two commercial antibodies against HNF1β: a goat polyclonal antibody from Santa Cruz Biotechnology (diluted 1:2000) and a rabbit antibody from Atlas Antibodies (diluted 1:300).
• Main results:
  • Ovarian clear cell carcinomas: nuclear staining in 12 of 14 with both antibodies. The 2 negative cases were the same with both antibodies.
  • Serous ovarian carcinomas: 5 of 26 stained with the Atlas antibody, versus 0 of 26 with the Santa Cruz antibody.
  • Malignant mesotheliomas (10) and reactive specimens (9): staining was uniformly negative with both antibodies.
  • Uterine clear cell carcinomas: both antibodies stained all 4.
  • Gastrointestinal, lung and breast adenocarcinomas: the Atlas antibody frequently stained them, most markedly the gastrointestinal carcinomas. Per Table 2, the Atlas antibody stained 9 of 10 gastrointestinal, 3 of 5 lung and 5 of 10 breast carcinomas.
  • The Santa Cruz antibody stained none of the 10 breast carcinomas but stained a substantial number of lung and gastrointestinal carcinomas. Per Table 2, it stained 3 of 5 lung and 6 of 10 gastrointestinal carcinomas.
  • The Santa Cruz antibody stained leukocytes in some specimens and produced background staining in others.
• The authors' conclusion: The author concluded that HNF1β may be of diagnostic value in differentiating clear cell from serous carcinoma in cases with proven genital origin, preferably together with a serous carcinoma marker such as WT1. The author also concluded that its role is questionable in distinguishing these tumors from adenocarcinomas of other origin, particularly in metastasis from an unknown primary tumor, given its frequent expression in carcinomas of nongenital origin.
• Limitations the authors state:
  • The author stated that future studies are needed to evaluate the sensitivity and specificity of the marker.
  • The author noted that telling clear cell carcinoma apart from mesothelial cells is rarely difficult even on morphology alone, which limits the practical value of that finding.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Carcinoma, Adenocarcinoma, Malignant Mesothelioma, Differential Diagnosis, Metastasis.

Related studies

• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin? — F.F. Gao, A.M. Krasinskas, et al. (2012)
• Cytomorphology of ovarian clear cell carcinomas in peritoneal effusions — D. Damiani, V. Suciu, et al. (2016)
• Rab25 is overexpressed in Müllerian serous carcinoma compared to malignant mesothelioma — K. Brusegard, H.T. Stavnes, et al. (2012)
• Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma — Y. Ohta, Y. Sasaki, et al. (2013)
• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)

Browse more research in Cancer Cytopathology, or return to medical research.